Proteomic cellular signatures of kinase inhibitor-induced cardiotoxicity

Abstract

AbstractDrug Toxicity Signature Generation Center (DToxS) at the Icahn School of Medicine at Mount Sinai is one of the centers for the NIH Library of Integrated Network-Based Cellular Signatures (LINCS) program. Its key aim is to generate proteomic and transcriptomic signatures that can predict cardiotoxic adverse effects of kinase inhibitors approved by the Food and Drug Administration. Towards this goal, high throughput shotgun proteomics experiments (308 cell line/drug combinations +64 control lysates) have been conducted. Using computational network analyses, these proteomic data can be integrated with transcriptomic signatures, generated in tandem, to identify cellular signatures of cardiotoxicity that may predict kinase inhibitor-induced toxicity and enable possible mitigation. Both raw and processed proteomics data have passed several quality control steps and been made publicly available on the PRIDE database. This broad protein kinase inhibitor-stimulated human cardiomyocyte proteomic data and signature set is valuable for prediction of drug toxicities.